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| 1 | Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)显示文摘Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC. | Yuankai Shi Lin Wu Xinmin Yu Puyuan Xing Yan Wang Jianying Zhou Airong Wang Jianhua Shi Yi Hu Ziping Wang Guangyu An Yong Fang Sanyuan Sun Caicun Zhou Changli Wang Feng Ye Xingya Li Junye Wang Mengzhao Wang Yunpeng Liu Yanqiu Zhao Ying Yuan Jifeng Feng Zhendong Chen Jindong Shi Tao Sun Gang Wu Yongqian Shu Qisen Guo Yi Zhang Yong Song Shucai Zhang Yuan Chen Wei Li Hongrui Niu Wenwei Hu Lijun Wang Jianan Huang Yang Zhang Ying Cheng Zhengdong Wu Bo Peng Jiya Sun Christoph Mancao Yanqi Wang Luyao Sun | 2022 | Cancer Communications2022，42，12： | 8 |
| 2 | Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer显示文摘Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be proven.Therefore,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer patients.We found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse model.Furthermore,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells.Among these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients. | Yan Xu Zheng Xiang Mohammed Alnaggar Léonce Kouakanou Jiawei Li Junyi He Jiashuang Yang Yi Hu Yan Chen Li Lin Jianlei Hao Jingxia Li Jibing Chen Man Li Qingling Wu Christian Peters Qinghua Zhou Jianshuang Li Yingqing Liang Xiaohua Wang Baohui Han Meili Ma Dieter Kabelitz Kecheng Xu Wenwei Tu Yangzhe Wu Zhinan Yin | 2021 | Cellular & Molecular Immunology2021，18，2： | 8 |
| 3 | Long term follow up of clinical outcome between patellar resurfacing and nonresurfacing in total knee arthroplasty: Chinese experience显示文摘 | Feng Bin Weng Xisheng Lin Jin Jin Jin Qian Wenwei Wang Wei Qiu Guixing | 2014 | Chinese Medical Journal2014，，22： | 7 |
| 4 | Response surface modeling-based source contribution analysis and VOC emission control policy assessment in a typical ozone-polluted urban Shunde,China显示文摘To develop a sound ozone(O_3) pollution control strategy,it is important to well understand and characterize the source contribution due to the complex chemical and physical formation processes of O_3.Using the 'Shunde' city as a pilot summer case study,we apply an innovative response surface modeling(RSM) methodology based on the Community Multi-Scale Air Quality(CMAQ) modeling simulations to identify the O_3 regime and provide dynamic analysis of the precursor contributions to effectively assess the O_3 impacts of volatile organic compound(VOC) control strategy.Our results show that Shunde is a typical VOC-limited urban O_3 polluted city.The 'Jiangmen' city,as the main upper wind area during July 2014,its VOCs and nitrogen oxides(NO_x) emissions make up the largest contribution(9.06%).On the contrary,the contribution from local(Shunde) emission is lowest(6.35%) among the seven neighbor regions.The local VOCs industrial source emission has the largest contribution comparing to other precursor emission sectors in Shunde.The results of dynamic source contribution analysis further show that the local NO_x control could slightly increase the ground O_3 under low(10.00%) and medium(40.00%)reduction ratios,while it could start to turn positive to decrease ground O_3 under the high NO_x abatement ratio(75.00%).The real-time assessment of O_3 impacts from VOCs control strategies in Pearl River Delta(PRD) shows that the joint regional VOCs emission control policy will effectively reduce the ground O_3 concentration in Shunde. | Zhiqiang You Yun Zhu Carey Jang Shuxiao Wang Jian Gao Che-Jen Lin Minhui Li Zhenghua Zhu Hao Wei Wenwei Yang | 2017 | Journal of Environmental Sciences2017，29，1： | 7 |
| 5 | Big Roles of Small Kinases:The Complex Functions of Receptor-Like Cytoplasmic Kinases in Plant Immunity and Development显示文摘Plants have evolved a large number of receptor-like cytoplasmic kinases(RLCKs)that often functionally and physically associate with receptor-like kinases(RLKs)to modulate plant growth,development and immune responses.Without any apparent extracellular domain,RLCKs relay intracellular signaling often via RLK complex-mediated transphosphorylation events.Recent advances have suggested essential roles of diverse RLCKs in concert with RLKs in regulating various cellular and physiological responses.We summarize here the complex roles of RLCKs in mediating plant immune responses and growth regulation,and discuss specifc and overlapping functions of RLCKs in transducing diverse signaling pathways. | Wenwei Lin Xiyu Ma Libo Shan Ping He | 2013 | Journal of Integrative Plant Biology2013，55，12： | 6 |
| 6 | GOLM1 exacerbates CD8^(+)T cell suppression in hepatocellular carcinoma by promoting exosomal PD-L1 transport into tumor-associated macrophages显示文摘The immunosuppressive microenvironment plays an important role in tumor progression and immunotherapy responses.Golgi membrane protein 1(GOLM1)is correlated to hepatocellular carcinoma(HCC)progression and metastasis.However,little is known about the role of GOLM1 in regulating the immunosuppressive environment and its impact on immunotherapeutic efficacy in HCC.In this study,GOLM1 was positively correlated with infiltrating tumor-associated macrophages(TAMs)expressed high levels of programmed death-ligand 1(PD-L1)and CD8^(+)T cell suppression in HCC tissues.Both gain-and loss-of-function studies determined a close correlation between GOLM1 and immunosuppression.In the mechanism,GOLM1 promoted COP9 signalosome 5-mediated PD-L1 deubiquitination in HCC cells and increased the transport of PD-L1 into exosomes via suppression of Rab27b expression.Furthermore,co-culture with exosomes derived from HCC cells upregulated the expression of PD-L1 on macrophages.Zoledronic acid in combination with anti-PD-L1 therapy reduced PD-L1^(+)TAMs infiltration and alleviated CD8^(+)T cell suppression,resulting in tumor growth inhibition in the mouse HCC model.Together,our study unveils a mechanism by which GOLM1 induces CD8^(+)T cells suppression through promoting PD-L1 stabilization and transporting PD-L1 into TAMs with exosome dependent.Targeting PD-L1^(+)TAM could be a novel strategy to enhance the efficacy of anti-PD-L1 therapy in HCC. | Jinhong Chen Zhifei Lin Lu Liu Rui Zhang Yan Geng Minghao Fan Wenwei Zhu Ming Lu Lu Lu Huliang Jia Jubo Zhang Lun-Xiu Qin | 2021 | Signal Transduction and Targeted Therapy2021，6，12： | 5 |
| 7 | Safety modeling and protection for lithium-ion batteries based on artificial neural networks method under mechanical abuse显示文摘The safety of lithium-ion batteries under mechanical abuse has become one of the major obstacles affecting the development of electric vehicles. In this paper, the lithium-ion battery safety model under mechanical abuse conditions is proposed by the Back Propagation Artificial Neural Network(BP-ANN) optimized by the Genetic Algorithm(GA). By experimental and simulation results, the proposed method can effectively predict battery mechanical properties. The corresponding correlation coefficient is greater than 0.99, the failure warning model has more safety margin, and the average security margin is greater than 29%. The multi-source warning weight shows that the mechanical soft short-circuit has the greatest warning margin, followed by that of the soft short-circuit of the electrical signal. The thermal soft short-circuit has the lowest warning margin because of the low thermal conductivity. The qualitative simulation results of the battery module reveal that, when electric vehicles are subjected to mechanical abuse conditions, the rapid reduction in the state-of-charge(SOC) of the rear batteries can effectively increase the reliability of the battery module. The proposed safety model is important to protect the safety and stability of lithium-ion batteries, which is conducive to promoting new energy vehicles and protecting the environment. | LI YiDing WANG WenWei LIN Cheng ZUO FengHao | 2021 | Science China(Technological Sciences)2021，64，11： | 3 |
| 8 | Mass‑Spring‑Damping Theory Based Equivalent Mechanical Model for Cylindrical Lithium‑ion Batteries under Mechanical Abuse显示文摘An equivalent mechanical model with the equivalent physical meaning of mass-spring-damping is proposed for cylindrical lithium-ion batteries through experiments and theory.The equivalent mechanical model of a cylindrical lithium-ion battery consists of a spring-damping parallel unit.Therefore,a spring-damping parallel unit connecting a damping unit in series is selected to construct the constitutive characteristics of the battery under mechanical abuse.Comparison results show that the equivalent mechanical model can more effectively describe the mechanical properties of the batteries than most cubic fitting models,of which the average relative error of the equivalent mechanical model under different states-of-charge is less than 6.75%.Combined with the proposed equivalent mechanical model,the failure process of the batteries was simulated and analyzed using LS-Dyna and HyperWorks.Under rigid rod tests,failure occurred at the core and bottom of the batteries;under hemispherical punch tests,failure occurred at the core and top,consistent with the experimental results.The average prediction error for the failure displacement under different abuse conditions is less than 4%in the simulations.The equivalent mechanical model requires only a few parameters and can be recognized easily.In the future,the model can be used in safety warning devices based on mechanical penetration. | Wenwei Wang Yiding Li Cheng Lin Sheng Yang | 2020 | Chinese Journal of Mechanical Engineering2020，33，2： | 3 |
| 9 | Tumor suppressor p53:new functions of an old protein显示文摘p53 was discovered 30 years ago.Extensive studies have been done on p53 since then,which makes p53 one of the most extensively studied genes.p53 has long been recognized as a key tumor suppressor.Cell cycle arrest,apoptosis and senescence have been traditionally recognized as the main functions of p53 in tumor suppression.Recently,some novel functions of p53 have been identified,including the regulation of energy metabolism,antioxidant defense,and microRNA expression and maturation,which all contribute to the role of p53 in tumor suppression.Furthermore,the contribution of p53 to normal biologic processes(e.g.reproduction and aging)and some other aspects of diseases(e.g.neurodegenerative diseases)is only now being appreciated.Here we will review recent advances in the study of some new functions of p53. | Zhaohui FENG Rui WU Meihua LIN Wenwei HU | 2011 | Frontiers in Biology2011，6，1： | 2 |
| 10 | Metamodel-Based Multi-Objective Reliable Optimization for Front Structure of Electric Vehicle显示文摘In this paper,a multi-objective reliable optimization(MORO)procedure for the front body of an electric vehicle is proposed and compared with determinate multi-objective optimization(DMOO).The energy absorption and peak crash force of the simplified vehicle model under the full-lap frontal impact condition are used as the design objectives,with the weighted sum of the basic frequency,the first-order torsional and bending frequencies of the full-size vehicle model,and the weight of the front body taken as the constraints.The thicknesses of nine components on the front body are defined as design variables,and their geometric tolerances determine the uncertainty factor.The most accurate metamodel using the polynomial response surface,kriging,and a radial basis function is selected to model four design criteria during optimization,allowing the efficiency improvement to be computed.Monte Carlo simulations are adopted to handle the probability constraints,and multi-objective particle swarm optimization is employed as the solver.The MORO results indicate reliability levels of R=100%,demonstrating the significant enhancement in reliability of the front body over that given by DMOO,and reliable design schemes and proposals are provided for further study. | Fengling Gao Shan Ren Cheng Lin Yingchun Bai Wenwei Wang | 2018 | Automotive Innovation2018，1，2： | 2 |
| 11 | Canonical forms for Hamiltonian and symplectic matrices and pencils显示文摘 | LIN Wenwei VOLKER Mehrmann | 1999 | Linear Algebra and its Appilcations1999，，： | 1 |
| 12 | Solutions to a quadratic inverse eigen-value problem 显示文摘 | CAI Yunfeng KUO Yuencheng LIN Wenwei | 2009 | Linear Algebra and Its Applications2009，430，： | 1 |
| 13 | Canonical forms for Hamiltonian and symplectic matrices and pencils显示文摘 | Lin Wenwei Volker Mehrmann | 1999 | Linear Algebra and its Applications1999，，： | 1 |
| 14 | An iterative algorithm for the solution of the discrete-time algebraic Riccati equation显示文摘 | Lu Linzhang Lin Wenwei | 1993 | Linear Algebra and Its Applications1993，，188189： | 1 |
| 15 | Direct ubiquiti- nation of pattern recognition receptor FLS2 attenuates plant in- nate immunity显示文摘 | Lu Dongping Lin Wenwei Gao Xiquan | 2011 | Science2011，332，6036： | 1 |
| 16 | MDIG-mediated H3K9me3 demethylation upregulates Myc by activating OTX2 and facilitates liver regeneration显示文摘The mineral dust-induced gene(MDIG)comprises a conserved JmjC domain and has the ability to demethylate histone H3 lysine 9 trimethylation(H3K9me3),Previous studies have indicated the significance of MDIG in promoting cell proliferation by modulating cell-cycle transition.However,its involvement in liver regeneration has not been extensively investigated.In this study,we generated mice with liver-specific knockout of MDIG and applied partial hepatectomy or carbon tetrachloride mouse models to investigate the biological contribution of MDIG in liver regeneration. | Jinpeng Du Wenwei Liao Haichuan Wang Guimin Hou Min Liao Lin Xu Jiwei Huang Kefei Yuan Xiangzheng Chen Yong Zeng | 2023 | Signal Transduction and Targeted Therapy2023，8，10： | 1 |
| 17 | Canonical forms for Hamiltonian and syrnplectic matrices and pencils显示文摘 | LIN WENWEI VOLKER MEHRMANN | 1999 | Linear Algebra and its Applications1999，，： | 1 |
| 18 | Canonical forms for Hamiltonian and symplectic matrices and pencils 显示文摘 | LIN WENWEI VOLKER MEHRMANN | 1999 | Linear Algebra and its Applications1999，，： | 1 |
| 19 | The role of human ADA2a in the regulation of p53 acetylation and stability显示文摘The tumor suppressor protein p53 is a well-known transcription factor that functions as a critical component of the genotoxic stress response via regulating the expression of effector proteins that control cellular fate following DNA damage. The human p300/CBP-associated factor(PCAF)-containing histone acetyltransferase(HAT) complex is important for the stability and activity of p53 via its acetylation. The human homolog of yeast alteration/deficiency in activation 2a(ADA2a) is a stable component of the human PCAF-containing HAT complex. In this study,we demonstrated that p53 and hADA2a physically interact with each other in human HEK 293T cells. Using overexpression and small interfering RNA-mediated knockdown,we demonstrated that hADA2a stabilizes p53 via promoting its acetylation at lysine 320 - a PCAF-dependent acetylation site. Furthermore,hADA2a can potentiate the transcriptional activity of p53 at the BAX and p21 promoters to induce cell apoptosis and cell cycle arrest. Overall,our results establish that hADA2a,a component of the PCAF-containing histone acetyltransferase co-activator complex,is a mediator of acetylation-dependent stabilization and activation of p53 in mammalian cells. | HUANG Jing ZHANG Li XIAO Lin XU LanJun HU FanLei SHAO WenWei LIU Wei MO XiaoNing SHI TaiPing QIU XiaoYan | 2011 | Chinese Science Bulletin2011，56，4： | 1 |
| 20 | Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1显示文摘 | Yue-Ming Wang Wenwei Lin Sergio C. Chai Jing Wu Su Sien Ong Erin G. Schuetz Taosheng Chen | 2013 | Toxicology and Applied Pharmacology2013，，： | 1 |
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